Age-dependent enhancement of inhibitory synaptic transmission in CA1 pyramidal neurons via GluR5 kainate receptors

Hippocampus ◽  
2009 ◽  
Vol 19 (8) ◽  
pp. 706-717 ◽  
Author(s):  
Changqing Xu ◽  
Changhai Cui ◽  
Daniel L. Alkon
Keyword(s):  
Synaptic Transmission ◽  
Pyramidal Neurons ◽  
Kainate Receptors ◽  
Inhibitory Synaptic Transmission ◽  
Ca1 Pyramidal Neurons ◽  
Age Dependent

scholarly journals Neuroligin3 splice isoforms shape inhibitory synaptic function in the mouse hippocampus

2020 ◽  
Vol 295 (25) ◽  
pp. 8589-8595 ◽  
Author(s):  
Motokazu Uchigashima ◽  
Ming Leung ◽  
Takuya Watanabe ◽  
Amy Cheung ◽  
Timmy Le ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Single Cell ◽  
Pyramidal Neurons ◽  
Autism Spectrum ◽  
Synaptic Function ◽  
Synaptic Activity ◽  
Dependent Manner ◽  
Splice Isoforms ◽  
Inhibitory Synaptic Transmission ◽  
Ca1 Pyramidal Neurons

Synapse formation is a dynamic process essential for the development and maturation of the neuronal circuitry in the brain. At the synaptic cleft, trans-synaptic protein–protein interactions are major biological determinants of proper synapse efficacy. The balance of excitatory and inhibitory synaptic transmission (E-I balance) stabilizes synaptic activity, and dysregulation of the E-I balance has been implicated in neurodevelopmental disorders, including autism spectrum disorders. However, the molecular mechanisms underlying the E-I balance remain to be elucidated. Here, using single-cell transcriptomics, immunohistochemistry, and electrophysiology approaches to murine CA1 pyramidal neurons obtained from organotypic hippocampal slice cultures, we investigate neuroligin (Nlgn) genes that encode a family of postsynaptic adhesion molecules known to shape excitatory and inhibitory synaptic function. We demonstrate that the NLGN3 protein differentially regulates inhibitory synaptic transmission in a splice isoform–dependent manner at hippocampal CA1 synapses. We also found that distinct subcellular localizations of the NLGN3 isoforms contribute to the functional differences observed among these isoforms. Finally, results from single-cell RNA-Seq analyses revealed that Nlgn1 and Nlgn3 are the major murine Nlgn genes and that the expression levels of the Nlgn splice isoforms are highly diverse in CA1 pyramidal neurons. Our results delineate isoform-specific effects of Nlgn genes on the E-I balance in the murine hippocampus.

scholarly journals Latrophilin-2 and latrophilin-3 are redundantly essential for parallel-fiber synapse function in cerebellum

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Roger Shen Zhang ◽  
Kif Liakath-Ali ◽  
Thomas C Südhof
Keyword(s):  
Synaptic Transmission ◽  
Purkinje Cells ◽  
Cerebellar Cortex ◽  
Pyramidal Neurons ◽  
Bergmann Glia ◽  
Parallel Fiber ◽  
Excitatory Synapses ◽  
Inhibitory Synaptic Transmission ◽  
Ca1 Pyramidal Neurons ◽  
Double Deletion

Latrophilin-2 (Lphn2) and latrophilin-3 (Lphn3) are adhesion GPCRs that serve as postsynaptic recognition molecules in CA1 pyramidal neurons of the hippocampus, where they are localized to distinct dendritic domains and are essential for different sets of excitatory synapses. Here, we studied Lphn2 and Lphn3 in the cerebellum. We show that latrophilins are abundantly and differentially expressed in the cerebellar cortex. Using conditional KO mice, we demonstrate that the Lphn2/3 double-deletion but not the deletion of Lphn2 or Lphn3 alone suppresses parallel-fiber synapses and reduces parallel-fiber synaptic transmission by ~50% without altering release probability. Climbing-fiber synapses, conversely, were unaffected. Even though ~50% of total cerebellar Lphn3 protein is expressed in Bergmann glia, Lphn3 deletion from Bergmann glia did not detectably impair excitatory or inhibitory synaptic transmission. Our studies demonstrate that Lphn2 and Lphn3 are selectively but redundantly required in Purkinje cells for parallel-fiber synapses.

scholarly journals Hypoxia Results in GABAergic Channelopathy

2005 ◽  
Vol 5 (6) ◽  
pp. 234-235 ◽  
Author(s):  
Nicholas P. Poolos
Keyword(s):  
Synaptic Transmission ◽  
Ampa Receptors ◽  
Pyramidal Neurons ◽  
Immature Brain ◽  
Fk 506 ◽  
Inhibitory Synaptic Transmission ◽  
Ca1 Pyramidal Neurons ◽  
Developing Rat ◽  
In Vivo Administration

AMPA/Kainate Receptor–mediated Downregulation of GABAergic Synaptic Transmission by Calcineurin after Seizures in the Developing Rat Brain Sanchez RM, Dai W, Levada RE, Lippman JJ, Jensen FE J Neurosci 2005;25:3442–3451 Hypoxia is the most common cause of perinatal seizures and can be refractory to conventional anticonvulsant drugs, suggesting an age-specific form of epileptogenesis. A model of hypoxia-induced seizures in immature rats reveals that seizures result in immediate activation of the phosphatase calcineurin (CaN) in area CA1 of hippocampus. After seizures, CA1 pyramidal neurons exhibit a downregulation of GABAA receptor (GABAAR)-mediated inhibition that was reversed by CaN inhibitors. CaN activation appears to be dependent on seizure-induced activation of Ca2+-permeable α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors (AMPARs), because the upregulation of CaN activation and GABAAR inhibition were attenuated by GYKI 52466 [1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine hydrochloride] or Joro spider toxin. GABAAR β2/3 subunit protein was dephosphorylated at 1 h after seizures, suggesting this subunit as a possible substrate of CaN in this model. Finally, in vivo administration of the CaN inhibitor FK-506 significantly suppressed hypoxic seizures, and posttreatment with NBQX (2,3-dihydroxy-6-nitro-7-sulfonylbenzo[ f]quinoxaline) or FK-506 blocked the hypoxic seizure-induced increase in CaN expression. These data suggest that Ca2+-permeable AMPARs and CaN regulate inhibitory synaptic transmission in a novel plasticity pathway that may play a role in epileptogenesis in the immature brain.

Protracted Postnatal Development of Inhibitory Synaptic Transmission in Rat Hippocampal Area CA1 Neurons

2000 ◽  
Vol 84 (5) ◽  
pp. 2465-2476 ◽  
Author(s):  
Akiva S. Cohen ◽  
Dean D. Lin ◽  
Douglas A. Coulter
Keyword(s):  
Synaptic Transmission ◽  
Postnatal Development ◽  
Pyramidal Neurons ◽  
Synaptic Function ◽  
Ca1 Neurons ◽  
Inhibitory Synaptic Transmission ◽  
The Third ◽  
Ca1 Pyramidal Neurons ◽  
Decay Times ◽  
And Function

In the CNS, inhibitory synaptic function undergoes profound transformation during early postnatal development. This is due to variations in the subunit composition of subsynaptic GABAA receptors (GABAARs) at differing developmental stages as well as other factors. These include changes in the driving force for chloride-mediated conductances as well as the quantity and/or cleft lifetime of released neurotransmitter. The present study was undertaken to investigate the nature and time course of developmental maturation of GABAergic synaptic function in hippocampal CA1 pyramidal neurons. In neonatal [postnatal day (P) 1–7] and immature (P8–14) CA1 neurons, miniature inhibitory postsynaptic currents (mIPSCs) were significantly larger, were less frequent, and had slower kinetics compared with mIPSCs recorded in more mature neurons. Adult mIPSC kinetics were achieved by the third postnatal week in CA1 neurons. However, despite this apparent maturation of mIPSC kinetics, significant differences in modulation of mIPSCs by allosteric agonists in adolescent (P15–21) neurons were still evident. Diazepam (1–300 nM) and zolpidem (200 nM) increased the amplitude of mIPSCs in adolescent but not adult neurons. Both drugs increased mIPSC decay times equally at both ages. These differential agonist effects on mIPSC amplitude suggest that in adolescent CA1 neurons, inhibitory synapses operate differently than adult synapses and function as if subsynaptic receptors are not fully occupied by quantal release of GABA. Rapid agonist application experiments on perisomatic patches pulled from adolescent neurons provided additional support for this hypothesis. In GABAAR currents recorded in these patches, benzodiazepine amplitude augmentation effects were evident only when nonsaturating GABA concentrations were applied. Furthermore nonstationary noise analysis of mIPSCs in P15–21 neurons revealed that zolpidem-induced mIPSC augmentation was not due to an increase in single-channel conductance of subsynaptic GABAARs but rather to an increase in the number of open channels responding to a single GABA quantum, further supporting the hypothesis that synaptic receptors may not be saturated during synaptic function in adolescent neurons. These data demonstrate that inhibitory synaptic transmission undergoes a markedly protracted postnatal maturation in rat CA1 pyramidal neurons. In the first two postnatal weeks, mIPSCs are large in amplitude, are slow, and occur infrequently. By the third postnatal week, mIPSCs have matured kinetically but retain distinct responses to modulatory drugs, possibly reflecting continued immaturity in synaptic structure and function persisting through adolescence.

scholarly journals Mu-opioids suppress GABAergic synaptic transmission onto orbitofrontal cortex pyramidal neurons with subregional selectivity

2020 ◽  
Author(s):  
Benjamin K. Lau ◽  
Brittany P. Ambrose ◽  
Catherine S. Thomas ◽  
Min Qiao ◽  
Stephanie L. Borgland
Keyword(s):  
Synaptic Transmission ◽  
Opioid Receptor ◽  
Orbitofrontal Cortex ◽  
Pyramidal Neurons ◽  
Mu Opioid Receptor ◽  
Mu Opioid ◽  
Inhibitory Synaptic Transmission ◽  
Receptor Coupling ◽  
Mu Opioids ◽  
Gabaergic Synaptic Transmission

AbstractThe orbitofrontal cortex (OFC) plays a critical role in evaluating outcomes in a changing environment. Administering opioids to the OFC can alter the hedonic reaction to food rewards and increase their consumption in a subregion specific manner. However, it is unknown how mu-opioid signalling influences synaptic transmission in the OFC. Thus, we investigated the cellular actions of mu-opioids within distinct subregions of the OFC. Using in-vitro patch clamp electrophysiology in brain slices containing the OFC, we found that the mu-opioid agonist, DAMGO produced a concentration-dependant inhibition of GABAergic synaptic transmission onto medial OFC (mOFC), but not lateral OFC (lOFC) neurons. This effect was mediated by presynaptic mu-opioid receptor activation of local parvalbumin (PV+)-expressing interneurons. The DAMGO-induced suppression of inhibition was long-lasting and not reversed upon washout of DAMGO, or by application of the mu-opioid receptor antagonist, CTAP, suggesting an inhibitory long-term depression (iLTD) induced by an exogenous mu-opioid. We show that LTD at inhibitory synapses is dependent on downstream cAMP/PKA signaling, which differs between the mOFC and lOFC. Finally, we demonstrate that endogenous opioid release triggered via moderate physiological stimulation can induce LTD. Taken together, these results suggest that presynaptic mu-opioid stimulation of local PV+ interneurons induces a long-lasting suppression of GABAergic synaptic transmission, which depends on subregional differences in mu-opioid receptor coupling to the downstream cAMP/PKA intracellular cascade. These findings provide mechanistic insight into the opposing functional effects produced by mu-opioids within the OFC.Significance StatementConsidering that both the OFC and the opioid system regulate reward, motivation, and food intake; understanding the role of opioid signaling within the OFC is fundamental for a mechanistic understanding of the sequelae for several psychiatric disorders. This study makes several novel observations. First, mu-opioids induce a long-lasting suppression of inhibitory synaptic transmission onto OFC pyramidal neurons in a regionally selective manner. Secondly, mu-opioids recruit PV+ inputs to suppress inhibitory synaptic transmission in the mOFC. Thirdly, the regional selectivity of mu-opioid action of endogenous opioids is due to the efficacy of mu-opioid receptor coupling to the downstream cAMP/PKA intracellular cascades. These experiments are the first to reveal a cellular mechanism of opioid action within the OFC.

Argiotoxin-636 blocks excitatory synaptic transmission in rat hippocampal CA1 pyramidal neurons

1989 ◽  
Vol 480 (1-2) ◽  
pp. 234-241 ◽  
Author(s):  
John H. Ashe ◽  
Charles L. Cox ◽  
Michael E. Adams
Keyword(s):  
Synaptic Transmission ◽  
Pyramidal Neurons ◽  
Excitatory Synaptic Transmission ◽  
Ca1 Pyramidal Neurons ◽  
Hippocampal Ca1
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